Crohn’s disease investigational treatment shows potential for achieving remission

Cedars-Sinai investigators have developed an investigational therapy that brought a significant number of patients with moderate to severe Crohn’s disease into remission, according to a new study published in The Lancet Gastroenterology & Hepatology. The findings from the international Phase II-A study suggest that a monoclonal antibody targeting a protein called TL1A could offer a new treatment option for patients with the disease.

The monoclonal antibody therapy, developed at Cedars-Sinai, is called tulisokibart. The experimental treatment also recently showed promising results in a separate Phase II study in treating ulcerative colitis.

Crohn’s disease and ulcerative colitis are chronic inflammatory bowel diseases that affect the digestive tract and impact approximately 1% of the U.S. population. There is no cure, and response to current treatments is variable.

“These findings, together with the recently published positive results in ulcerative colitis, strongly support this approach as a completely new therapy for people with inflammatory bowel diseases,” said clinician-scientist and geneticist Dermot McGovern, MD, Ph.D., director of Translational Research in the F. Widjaja Inflammatory Bowel Disease Institute at Cedars-Sinai and senior author of the study.

McGovern, the Joshua L. and Lisa Z. Greer Chair in Inflammatory Bowel Disease Genetics and the director of Precision Health at Cedars-Sinai, together with colleagues at Cedars-Sinai, helped develop tulisokibart.

“This mechanism was identified through both genetic and immunological work, the vast majority of which came from the inflammatory bowel diseases group at Cedars-Sinai,” he said.

In the Phase II-A trial, called APOLLO-CD, 55 adults with Crohn’s disease received tulisokibart in varying doses over 12 weeks. The results showed that nearly 50% of patients achieved clinical remission, compared to about 16% in historical studies.

The investigational therapy also may target fibrosis—a process that leads to narrowing in the gut and often requires surgery. Fibrosis is a major problem in Crohn’s disease and other diseases and cannot currently be prevented or reversed.

Stephan Targan, MD, former executive director of the F. Widjaja Inflammatory Bowel Disease Institute at Cedars-Sinai and a study author, said the therapy’s ability to target fibrosis has broad implications.

“Fibrosis is a major issue in many chronic medical conditions and can cause serious complications,” said Targan, the Feintech Family Chair in Inflammatory Bowel Disease. “So, there is great interest in seeing whether the drug we developed may have benefits even beyond inflammatory bowel disease.”

McGovern added that data from the APOLLO-CD study indicated that response to tulisokibart was rapid—patients’ inflammatory markers dropped within a week of beginning the therapy.

“This is promising news, because in addition to getting people well and helping them stay in remission, we want to help them get well as quickly as possible,” he said.

Also promising: Tulisokibart was developed with a diagnostic tool to help identify people who are most likely to benefit from the drug, which would introduce precision medicine to inflammatory bowel disease care.

McGovern, Targan and a team of researchers at Cedars-Sinai, including Janine Bilsborough, Ph.D., director of Inflammatory Bowel Disease Drug Discovery and Development, have long studied the role of TL1A in contributing to inflammation and fibrosis in inflammatory bowel disease patients.

Bilsborough, also a study author, said, “We’ve dedicated our careers to pursuing innovative therapies for people affected by inflammatory bowel disease. It’s very fulfilling to see scientific progress that could help Crohn’s and ulcerative colitis patients reach lasting remission and live a life without limitation.”

Further studies are in progress in larger groups of people with both Crohn’s disease and ulcerative colitis: The double-blind, placebo-controlled Phase III trials will determine the effectiveness and safety of tulisokibart as a treatment to bring about and maintain remission in people with IBD.

Phase II results suggest targeted therapy is effective for moderate to severe ulcerative colitis